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To investigate the relative effect of disorganization of the retinal inner layers (DRIL) and ellipsoid zone (EZ) loss on visual function in diabetic macular ischemia (DMI).Prospective cross-sectional observational study.Patients with stable treated proliferative diabetic retinopathy (PDR) without center-involved diabetic macular edema were recruited at the Moorfields Eye Hospital from December 2019 to November 2021. The main inclusion criteria were best-corrected visual acuity (BCVA) of ≥ 40 ETDRS letters (Snellen equivalent 20/160) with OCT angiography (OCTA) evidence of DMI in ≥ 1 eye.Each eligible eye of the recruited patients was assessed for BCVA, OCT, and OCTA metrics. The prespecified OCT parameters were DRIL and subfoveal EZ loss. Generalized estimating equations were used.The frequency of DRIL and EZ loss, their relative contributions to vision loss, and their associations with microvascular alterations were evaluated.A total of 125 eyes of 86 patients with PDR were enrolled; 104 (83%) eyes had a BCVA of ≥ 70 letters. Disorganization of the retinal inner layers was more prevalent than EZ loss (46% [58 eyes] vs. 19% [24 eyes]). On average, the presence of DRIL had a more pronounced impact on vision, retinal thickness, and microvascular parameters than EZ loss. After multivariable adjustment, the odds of coexisting DRIL increased by 12% with every letter decrease in BCVA; however, there was no statistically significant association of subfoveal EZ loss with BCVA. In eyes with DRIL in the absence of EZ loss, the BCVA declined significantly by 6.67 letters compared with eyes with no DRIL nor EZ loss (95% confidence interval [CI], -9.92 to -3.41; P0.001). However, if DRIL and EZ loss coexisted, the resultant BCVA was 13.22 letters less than eyes without these structural abnormalities (95% CI, -18.85 to -7.59; P0.001).In patients with DMI with a Snellen visual acuity of 20/160 or better, eyes with DRIL were associated with more visual function loss and retinal blood circulation alterations than those with subfoveal EZ loss only.

Geographic atrophy (GA) is currently an untreatable condition. Emerging evidence from recent clinical trials show that anti-complement therapy may be a successful treatment option. However, several trials in this therapy area have failed as well. This raises several questions. Firstly, does complement therapy work for all patients with GA? Secondly, is GA one disease? Can we assume that these failed clinical trials are due to ineffective interventions or are they due to flawed clinical trial designs, heterogeneity in GA progression rates or differences in study cohorts? In this article we try to answer these questions by providing an overview of the challenges of designing and interpreting outcomes of randomised controlled trials (RCTs) in GA. These include differing inclusion-exclusion criteria, heterogeneous progression rates of the disease, outcome choices and confounders.摘要: 地图样萎缩 (Geographic atrophy, GA) 是一种目前尚无法治愈的疾病。最近来自临床试验的新兴证据表明, 抗补体治疗可能成为一种有效的治疗方式。然而, 基于该治疗方式的几项试验都失败了。这就提出了几个问题。首先, 补体治疗是否适用于所有GA患者? 其次, GA是一种疾病吗? 我们是否可以提出几个假设: 这些临床试验失败是因为干预措施无效还是因为临床试验设计有缺陷? GA进展率是否具有异质性或研究队列内是否存在差异? 在本文中, 我们总结了这些GA随机对照试验 (RCT) 在试验设计和结果解读中面临的挑战, 其中包括不同的纳入-排除标准、疾病的异质性进展率、结局选择和混杂因素, 并试图以此来回答这些问题。.

Diabetic Retinopathy (DR) is a leading cause of preventable visual impairment in the working age population. Despite the increasing prevalence of DR, there remain gaps in our understanding of its pathophysiology. This is a prospective case-control study comparing the genetic profiles of patients with no DR vs. non-proliferative DR (NPDR) focusing on intraretinal microvascular abnormalities (IRMA) and venous beading (VB) in Caucasians. A total of 596 participants were recruited to the study; 199 with moderate/severe NPDR and 397 with diabetes for at least 5 years without DR. Sixty-four patients were excluded due to technical issues. In total, 532 were analysed; 181 and 351 were in the NPDR group and no DR group, respectively. Those with severe IRMA and VB had distinctly different genetic profiles from each other and from the no DR group, which further supports the theory that these two features of DR might have different etiologies. This also suggests that IRMA and VB are independent risk factors for the development of PDR and may have different pathophysiologies. If these findings are confirmed in larger studies, this could pave the way for personalised treatment options for those more at risk of developing different features of NPDR.

Aims To estimate the incidence of early treatment diabetic retinopathy study (ETDRS) level 47 and 53 and progression to treatment with panretinal photocoagulation (PRP) for proliferative DR (PDR). Methods Log-linear regression was used to estimate the incidence of level 47–53 or worse for 33,009 people with diabetes (PWD) in Gloucestershire during 2013–2016 by calendar year and diabetes type, based on the first recording. Progression was analysed in Gloucestershire and Bristol with a parametric survival analysis examining the association of baseline and time-varying demographic and clinical factors on time to PRP after the first recording of level 47–53. Results Incidence decreased from 0.57 (95% confidence intervals (CI) 0.48–0.67) per 100 PWD in 2013 to 0.35 (95% CI 0.29–0.43) in 2016 (p 1c were associated with an increase in the risk of initiating PRP (hazard ratio 3.14 (95% CI: 1.60–6.15) and 1.21 (95% CI: 1.06–1.38 per 10 mmol/mol) respectively). Conclusion This study provides additional understanding of this population and shows that a high proportion of patients with ETDRS levels 47–53 need to be monitored as they are at high risk of progressing to PDR.

Purpose The increasing diabetes prevalence and advent of new treatments for its major visual-threatening complications (diabetic macular edema [DME] and proliferative diabetic retinopathy [PDR]), which require frequent life-long follow-up, have increased hospital demands markedly. Subsequent delays in patient's evaluation and treatment are causing sight loss. Strategies to increase capacity are needed urgently. The retinopathy (EMERALD) study tested diagnostic accuracy, acceptability, and costs of a new health care pathway for people with previously treated DME or PDR. Design Prospective, multicenter, case-referent, cross-sectional, diagnostic accuracy study undertaken in 13 hospitals in the United Kingdom. Participants Adults with type 1 or 2 diabetes previously successfully treated DME or PDR who, at the time of enrollment, had active or inactive disease. Methods A new health care pathway entailing multimodal imaging (spectral-domain OCT for DME, and 7-field Early Treatment Diabetic Retinopathy Study [ETDRS] and ultra-widefield [UWF] fundus images for PDR) interpreted by trained nonmedical staff (ophthalmic graders) to detect reactivation of disease was compared with the current standard care (face-to-face examination by ophthalmologists). Main Outcome Measures Primary outcome: sensitivity of the new pathway. Secondary outcomes: specificity; agreement between pathways; costs; acceptability; proportions requiring subsequent ophthalmologist assessment, unable to undergo imaging, and with inadequate images or indeterminate findings. Results The new pathway showed sensitivity of 97% (95% confidence interval [CI], 92%–99%) and specificity of 31% (95% CI, 23%–40%) to detect DME. For PDR, sensitivity and specificity using 7-field ETDRS images (85% [95% CI, 77%–91%] and 48% [95% CI, 41%–56%], respectively) or UWF images (83% [95% CI, 75%–89%] and 54% [95% CI, 46%–61%], respectively) were comparable. For detection of high-risk PDR, sensitivity and specificity were higher when using UWF images (87% [95% CI, 78%–93%] and 49% [95% CI, 42%–56%], respectively, for UWF versus 80% [95% CI, 69–88%] and 40% [95% CI, 34%–47%], respectively, for 7-field ETDRS images). Participants preferred ophthalmologists’ assessments; in their absence, they preferred immediate feedback by graders, maintaining periodic ophthalmologist evaluations. When compared with the current standard of care, the new pathway could save £1390 per 100 DME visits and between £461 and £1189 per 100 PDR visits. Conclusions The new pathway has acceptable sensitivity and would release resources. Users’ suggestions should guide implementation.

Geographic atrophy (GA) secondary to age-related macular degeneration accounts for close to one-quarter of cases of legal blindness in the USA and the UK. Despite this notable disease burden, the pathophysiology of GA is complex and not fully understood, and there is currently no approved treatment to prevent or slow its progression. GA is heterogeneous in its appearance and extent, and underlying associated traits such as drusen and complement factor polymorphisms vary between patients and by ethnicity, posing a challenge for treatment development. The root cause of vision loss in GA is photoreceptor death; therefore, protecting photoreceptors from damage and delaying their degeneration are key to successful GA treatment. There are multiple neuroprotective pathways that may contribute to protecting photoreceptors from damage, and compounds that target these pathways include antioxidants, neurotrophic factors, and catalases. However, the efficacy of previously trialled neuroprotective therapies in GA, such as brimonidine, tandospirone, and NT-501, has been inconsistent; this may be due to their target of action, method of delivery, and/or suboptimal duration of action. Neurotrophic factors, or molecules involved in neuroprotective signalling cascades, may be ideal agents for further investigation for the treatment of GA. Future neuroprotective strategies in GA must focus on the development of agents with a long duration of action that can combat the progression of chronic damage in GA to provide clinically meaningful benefits for patients.

Diabetic macular ischemia (DMI) is a common complication of diabetic retinopathy that can lead to progressive and irreversible visual loss. Despite substantial clinical burden, there are no treatments for DMI, no validated clinical trial endpoints, and few clinical trials focusing on DMI. Therefore, generating consensus on validated endpoints that can be used in DMI for the development of effective interventions is vital. In this review, we discuss potential endpoints appropriate for use in clinical trials of DMI, and consider the data required to establish acceptable and meaningful endpoints. A combination of anatomical, functional, and patient-reported outcome measures will provide the most complete picture of changes that occur during the progression of DMI. Potential endpoint measures include change in size of the foveal avascular zone measured by optical coherence tomography angiography and change over time in best-corrected visual acuity. However, these endpoints must be supported by further research. We also recommend studies to investigate the natural history and progression of DMI. In addition to improving understanding of how patient demographics and comorbidities such as diabetic macular edema affect clinical trial endpoints, these studies would help to build the consensus definition of DMI that is currently missing from clinical practice and research.

OBJECTIVE To compare four screening strategies for diabetic macular edema (DME). RESEARCH DESIGN AND METHODS Patients attending diabetic retinopathy screening were recruited and received macular optical coherence tomography (OCT), in addition to visual acuity (VA) and fundus photography (FP) assessments, as part of the standard protocol. Two retina specialists provided the reference grading by independently assessing each subject’s screened data for DME. The current standard protocol (strategy A) was compared for sensitivity, specificity, quality-adjusted life-year (QALY) gained, and incremental cost-effectiveness ratio (ICER) with three alternative candidate protocols using a simulation model with the same subjects. In strategy B, macular hemorrhage or microaneurysm on FP were removed as surrogate markers for possible DME. Strategy C used best-corrected instead of habitual/pinhole VA and added central subfield thickness (CST) >290 μm on OCT in suspected cases as a confirmation marker for possible DME. Strategy D used CST >290 μm OCT in all subjects as a surrogate marker for suspected DME. RESULTS We recruited 2,277 subjects (mean age 62.80 ± 11.75 years, 43.7% male). The sensitivities and specificities were 40.95% and 86.60%, 22.86% and 95.63%, 32.38% and 100%, and 74.47% and 98.34% for strategies A, B, C, and D, respectively. The costs (in U.S. dollars) of each QALY gained for strategies A, B, C, and D were $7,447.50, $8,428.70, $5,992.30, and $4,113.50, respectively. CONCLUSIONS The high false-positive rate of the current protocol generates unnecessary referrals, which are inconvenient for patients and costly for society. Incorporating universal OCT for screening DME can reduce false-positive results by eightfold, while improving sensitivity and long-term cost-effectiveness.

Purpose Approximately 50% of patients receiving anti–vascular endothelial growth factor (VEGF) therapy show significant improvement in diabetic retinopathy severity score (DRSS), in particular at DRSS level 47 to 53 (moderately severe to severe nonproliferative diabetic retinopathy). Level 47 to 53 consists of 3 main features: deep hemorrhages (DH), venous beading (VB), and intraretinal microvascular abnormalities (IRMAs). It is unclear whether these features respond to anti-VEGF therapies differently. Design Post hoc analysis of Intravitreal Aflibercept versus Panretinal Photocoagulation in Patients with Proliferative Diabetic Retinopathy (CLARITY) study. Participants Treatment-naive participants randomized to intravitreal aflibercept. Methods We reanalyzed the fundus images at baseline, week 12, and week 52 to assess the changes of the 3 main features in DRSS level 47 to 53 in those patients who were treatment naive and had received aflibercept. Main Outcome Measures Changes in DH, VB, and IRMA after aflibercept therapy at weeks 12 and 52. Results Fifty-five treatment-naive eyes at baseline that received aflibercept were included in the study. Severe DH and severe IRMA improved in approximately 75% of eyes at week 12 and mostly remained improved at week 52; VB remained unchanged in all eyes at week 12. From 12 weeks, 32 eyes that had received injections showed improved or stable DH compared with 7 eyes that did not receive injections, and DH deteriorated in 6 eyes with no further injections compared with 4 eyes that had received more injections (P = 0.0072). Similarly, 15 eyes that continued to receive injections from week 12 showed improved or stable IRMA compared with 4 who did not receive injections (P = 0.006). Worsening of IRMA was seen in 5 eyes with no further injections compared with 4 eyes that continued to receive injections. The improvements in DH and IRMA are more likely to be maintained if less than 16 weeks have elapsed since the last anti-VEGF injection. Conclusions Aflibercept seems to improve DH and IRMA after just 3 injections. As soon as the frequency of injections were reduced, DH and IRMA can deteriorate again. It is unclear whether these results can be translated to patients without PDR.

Purpose To describe the defining features of incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA), a consensus term referring to the OCT-based anatomic changes often identified before the development of complete RPE and outer retinal atrophy (cRORA) in age-related macular degeneration (AMD). We provide descriptive OCT and histologic examples of disease progression. Design Consensus meeting. Participants Panel of retina specialists, including retinal imaging experts, reading center leaders, and retinal histologists. Methods As part of the Classification of Atrophy Meeting (CAM) program, an international group of experts analyzed and discussed longitudinal multimodal imaging of eyes with AMD. Consensus was reached on a classification system for OCT-based structural alterations that occurred before the development of atrophy secondary to AMD. New terms of iRORA and cRORA were defined. This report describes in detail the CAM consensus on iRORA. Main Outcome Measures Defining the term iRORA through OCT imaging and longitudinal cases showing progression of atrophy, with histologic correlates. Results OCT was used in cases of early and intermediate AMD as the base imaging method to identify cases of iRORA. In the context of drusen, iRORA is defined on OCT as (1) a region of signal hypertransmission into the choroid, (2) a corresponding zone of attenuation or disruption of the RPE, and (3) evidence of overlying photoreceptor degeneration. The term iRORA should not be used when there is an RPE tear. Longitudinal studies confirmed the concept of progression from iRORA to cRORA. Conclusions An international consensus classification for OCT-defined anatomic features of iRORA are described and examples of longitudinal progression to cRORA are provided. The ability to identify these OCT changes reproducibly is essential to understand better the natural history of the disease, to identify high-risk signs of progression, and to study early interventions. Longitudinal data are required to quantify the implied risk of vision loss associated with these terms. The CAM classification provides initial definitions to enable these future endeavors, acknowledging that the classification will be refined as new data are generated.

Purpose\ud To estimate prevalence and incidence of diabetic retinopathy (DR) in a UK region by severity between 2012 and 2016 and risk factors for progression to proliferative DR (PDR).\ud \ud Methods\ud Electronic medical records from people with diabetes (PWD) ≥18 years seen at the Gloucestershire Diabetic Eye Screening Programme (GDESP) and the hospital eye clinic were analysed (HEC). Prevalence and incidence of DR per 100 PWD (%) by calendar year, grade and diabetes type were estimated using log-linear regression. Progression to PDR and associated risk factors were estimated using parametric survival analyses.\ud \ud Results\ud Across the study period, 35 873 PWD had at least one DR assessment. They were aged 66 (56–75) years (median (interquartile range)), 57% male, 5 (1–10) years since diabetes diagnosis, 93% Type 2 diabetes. Prevalence of DR decreased from 38.9% (95% CI: 38.1%, 39.8%) in 2012 to 36.6% (95% CI: 35.9%, 37.3%) in 2016 (p < 0.001). Incidence of any DR decreased from 10.9% (95% CI: 10.4%, 11.5%) in 2013 to 8.5% (95% CI: 8.1%, 9.0%) in 2016 (p < 0.001). Prevalence of PDR decreased from 3.5% (95% CI: 3.3%, 3.8%) in 2012 to 3.1% (95% CI 2.9%, 3.3%) in 2016 (p = 0.008). Incidence of PDR did not change over time. HbA1c and bilateral moderate–severe NPDR were statistically significant risk factors associated with progression to PDR.\ud \ud Conclusions\ud Incidence and prevalence of DR decreased between 2012 and 2016 in this well-characterized population of the UK.

Age-related macular degeneration (AMD) is a leading cause of blindness. Late AMD can be classified into exudative (commonly known as wet AMD [wAMD]) or dry AMD, both of which may progress to macular atrophy (MA). MA causes irreversible vision loss and currently has no approved pharmacological treatment. The standard of care for wAMD is treatment with anti-vascular endothelial growth factors (VEGFs). However, recent evidence suggests that anti-VEGF treatment may play a role in the development of MA. Therefore, it is important to identify risk factors for the development of MA in patients with wAMD. For example, excessive blockade of VEGF through intense use of anti-VEGF agents may accelerate the development of MA. Patients with type III macular neovascularization (retinal angiomatous proliferation) have a particularly high risk of MA. These patients are characterized as having a pre-existing thin choroid (age-related choroidopathy), suggesting that the choroidal circulation is unable to respond to increased VEGF expression. Evidence suggests that subretinal fluid (possibly indicative of residual VEGF activity) may play a protective role. Patients receiving anti-VEGF agents must be assessed for overall risk of MA, and there is an unmet medical need to prevent the development of MA without undertreating wAMD.

PurposeTo compare the efficacy and safety of subthreshold micropulse laser (SML) with threshold conventional laser (TCL) in central serous chorioretinopathy (CSC).MethodsProspective, randomized, double-masked, non-inferiority, 12-week clinical trial. Patients were randomly assigned 1:1 to SML group or TCL group. Patients in the SML group were treated with 577 nm micropulse laser. The spot size was 160 µm, the duty cycle was 5% and exposure time was 0.2 s. The power was 50% threshold tested. Patients in the TCL group were treated with 577 nm continuous laser. The power was 100% threshold tested. The primary outcome was the mean change in best-corrected visual acuity (BCVA) at week 12, with a non-inferiority limit of five letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts.ResultsEighty-eight patients were enroled. Seventy-seven patients were male. Forty-four patients were in SML group and 44 in TCL group. At week 12, SML was equivalent to TCL with a gain of 6.23 ± 8.59 and 6.61 ± 6.35 letters, respectively, (SML–TCL difference: −0.38 letters; 95% confidence interval (CI):−3.58–2.81;Pnon-inferiority = 0.0026). There was no statistically significant difference between the two groups (t = 0.240,P = 0.811). At week 12, the proportion of patients whose SRF had been totally absorbed was 63.63 and 81.82% respectively for SML and TCL groups. There was no statistically significant difference between the two groups (χ2 = 3.67,P = 0.056).ConclusionsBoth SML and TCL can improve visual acuity in CSC. SML was non-inferior to TCL in the improvement of BCVA.

Background: Diabetic macular oedema (DMO) is effectively treated with ranibizumab but multiple injections are required. Where there is also peripheral ischaemia, it has been promoted that targeted panretinal photocoagulation (PRP) may reduce the number of injections. Method: Patients with optical coherence tomography confirmed DMO and Ultra-widefield Fundus Fluorescein Angiography confirmed peripheral retinal ischaemia were randomised to PRP plus ranibizumab or ranibizumab monotherapy. After three injections, repeat injections were given until the visual acuity was stable and the macula was dry. Re-treatment was given if there was a drop of visual acuity and/or a recurrence of intra-retinal fluid. The primary outcome was the number of repeat injections required after the first 6 months up until 1 year. Results: There were 49 patients, 25 in the ranibizumab only group and 24 in the ranibizumab + PRP group recruited at seven UK sites. The average number of injections in the ranibizumab-only arm was 6.84 over 1 year and 2.52 between months 6 and 12. The average number of injections in the combined arm was 6.67, with the number of injections in the second 6 months 1.92. For the primary outcome, comparing the number of 6- to 12-month injections, the result was not statistically significant (p = 0.33). Conclusion: The addition of targeted PRP to areas of non-perfusion in a patient with DMO does not reduce the number of injections required in the first year. It seems most likely that local VEGF at the macula is the main cause of DMO.

Background/aimsSurveillance of people with previously successfully treated diabetic macular oedema (DMO) and proliferative diabetic retinopathy (PDR) adds pressure on ophthalmology services. This study evaluated a new surveillance pathway entailing multimodal imaging reviewed by trained ophthalmic graders and compared it with the current standard care (face-to-face evaluation by an ophthalmologist).MethodsCost analysis of the new ophthalmic grader pathway, compared with the standard of care, from the perspective of the UK National Health Service, based on evidence from the Effectiveness of Multimodal imaging for the Evaluation of Retinal oedema And new vesseLs in Diabetic retinopathy study. Resource use data were prospectively obtained including times to undertake each procedure. Effectiveness was assessed in terms of sensitivity and specificity of referral decisions in the grader pathway. Costs (SDs) were analysed per 100 patients separately for DMO and PDR at 2018/2019 costs.ResultsFor DMO, where sensitivity was very high (97%), the cost difference (savings) for the grader’s pathway would be £1390 per 100 patients. For PDR, the cost would be reduced by £461 for seven-field Early Treatment for Diabetic Retinopathy Study (ETDRS) images and by £1889 for ultrawide field images, per 100 patients. Ultrawide images required less time to be obtained and read than seven-field ETDRS. The real savings would be in ophthalmologist time, which could be then redirected to the evaluation of people at high risk of visual loss.ConclusionsSurveillance of people with previously successfully treated DMO and PDR by trained ophthalmic graders can achieve satisfactory results and release ophthalmologist time.Trial registration numbersNCT03490318,ISRCTN10856638.

Owing to the increasing prevalence of diabetes, the workload related to diabetic macular oedema and proliferative diabetic retinopathy is rising, making it difficult for hospital eye services to meet demands.The objective was to evaluate the diagnostic performance, cost-effectiveness and acceptability of a new pathway using multimodal imaging interpreted by ophthalmic graders to detect reactivation of diabetic macular oedema/proliferative diabetic retinopathy in previously treated patients.This was a prospective, case-referent, cross-sectional diagnostic study.The setting was ophthalmic clinics in 13 NHS hospitals.Adults with type 1 or type 2 diabetes with previously successfully treated diabetic macular oedema/proliferative diabetic retinopathy in one/both eyes in whom, at the time of enrolment, diabetic macular oedema/proliferative diabetic retinopathy could be active or inactive.For the ophthalmic grader pathway, review of the spectral domain optical coherence tomography scans to detect diabetic macular oedema, and seven-field Early Treatment Diabetic Retinopathy Study/ultra-wide field fundus images to detect proliferative diabetic retinopathy, by trained ophthalmic graders. For the current standard care pathway (reference standard), ophthalmologists examined patients face to face by slit-lamp biomicroscopy for proliferative diabetic retinopathy and, in addition, spectral domain optical coherence tomography imaging for diabetic macular oedema.The primary outcome measure was sensitivity of the ophthalmic grader pathway to detect active diabetic macular oedema/proliferative diabetic retinopathy. The secondary outcomes were specificity, agreement between pathways, cost-consequences, acceptability and the proportion of patients requiring subsequent ophthalmologist assessment, unable to undergo imaging and with inadequate quality images/indeterminate findings. It was assumed for the main analysis that all patients in whom graders diagnosed active disease or were 'unsure' or images were 'ungradable' required examination by an ophthalmologist.Eligible participants with active and inactive diabetic macular oedema (152 and 120 participants, respectively) and active and inactive proliferative diabetic retinopathy (111 and 170 participants, respectively) were recruited. Under the main analysis, graders had a sensitivity of 97% (142/147) (95% confidence interval 92% to 99%) and specificity of 31% (35/113) (95% confidence interval 23% to 40%) to detect diabetic macular oedema. For proliferative diabetic retinopathy, graders had a similar sensitivity and specificity using seven-field Early Treatment Diabetic Retinopathy Study [sensitivity 85% (87/102), 95% confidence interval 77% to 91%; specificity 48% (77/160), 95% confidence interval 41% to 56%] or ultra-wide field imaging [sensitivity 83% (87/105), 95% confidence interval 75% to 89%; specificity 54% (86/160), 95% confidence interval 46% to 61%]. Participants attending focus groups expressed preference for face-to-face evaluations by ophthalmologists. In the ophthalmologists' absence, patients voiced the need for immediate feedback following grader's assessments, maintaining periodic evaluations by ophthalmologists. Graders and ophthalmologists were supportive of the new pathway. When compared with the reference standard (current standard pathway), the new grader pathway could save £1390 per 100 patients in the review of people with diabetic macular oedema and, depending on the imaging modality used, between £461 and £1189 per 100 patients in the review of people with proliferative diabetic retinopathy.For people with diabetic macular oedema, the ophthalmic grader pathway appears safe and cost saving. The sensitivity of the new pathway to detect active proliferative diabetic retinopathy was lower, but may still be considered acceptable for patients with proliferative diabetic retinopathy previously treated with laser. Suggestions from focus group discussions should be taken into consideration if the new pathway is introduced to ensure its acceptability to users.Lack of fundus fluorescein angiography to confirm diagnosis of active proliferative diabetic retinopathy.Could refinement of the new pathway increase its sensitivity to detect proliferative diabetic retinopathy? Could artificial intelligence be used for automated reading of images in this previously treated population?Current Controlled Trials ISRCTN10856638 and ClinicalTrials.gov NCT03490318.This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inMore and more people are developing diabetes. Diabetic macular oedema and proliferative diabetic retinopathy are complications of diabetes, which could cause blindness. Thus, people with diabetic macular oedema and proliferative diabetic retinopathy need to be treated in a timely manner and reviewed in clinic for life. The population in the world is ageing. As a result, there are more people with eye diseases. There are also more treatments now for people with eye diseases. The workload in hospitals is increasing, making it difficult for the NHS to cope with the demand. There are not enough ophthalmologists (eye doctors) to look after patients. Delayed appointments and treatment mean that patients may lose sight. The goal of EMERALD (Effectiveness of Multimodal imaging for the Evaluation of Retinal oedema And new vesseLs in Diabetic retinopathy) was to see if patients with treated and stable diabetic macular oedema or proliferative diabetic retinopathy could be followed by ‘ophthalmic graders’, who are not doctors but are trained to diagnose diabetic macular oedema and proliferative diabetic retinopathy. In EMERALD, trained ophthalmic graders examined photographs of the back of the eye of people with diabetic macular oedema and proliferative diabetic retinopathy. They checked if diabetic macular oedema and proliferative diabetic retinopathy remain inactive. If so, patients could continue follow-up with the ophthalmic graders. If diabetic macular oedema or proliferative diabetic retinopathy were active, graders would immediately refer patients to ophthalmologists. EMERALD found that graders were excellent at detecting diabetic macular oedema, and this could give ophthalmologists time to see other patients. Graders were not quite as good at detecting active proliferative diabetic retinopathy. However, considering that patients had already had treatment, this may still be safe. Patients participating in focus group discussions mentioned that they would prefer to see ophthalmologists, so they could ask questions about their eye condition. If this was not possible, they would like to have immediate results from graders and still see the ophthalmologist from time to time.

Purpose Patients with center-involved diabetic macular edema (CI-DME) with good visual acuity (VA) represent a controversial clinical scenario in which a subthreshold laser might be a reasonable approach. We report a case series of patients with CI-DME with VA better than 20/32 who were treated with a subthreshold 577 nm (yellow) laser. Methods The area of retinal thickening on OCT was treated with confluent laser spots at individually titrated power. The fovea was spared from treatment. Effectiveness and safety were evaluated through OCT and autofluorescence (AF) as well as BCVA. Results A total of 23 eyes from 19 patients were treated. VA ranged from 20/20 to 20/30. The follow-up period ranged from 6 to 18 months. Edema in OCT resolved completely at the end of follow-up in 56.5% (13/23) of the cases. Central retinal thickness was reduced at 12 weeks and at the end of follow-up, with a mean reduction of 16.9 μm and 22 μm, respectively (paired t-test p = 0.001 and 0.0003). VA remained stable. The laser was invisible (OCT, AF, Fundoscopy) in 91,3% (21/23) of eyes. Conclusions A fovea-sparing yellow subthreshold laser was safe and effective for treating CI-DME patients with good VA in this case series. This technique is of interest to prevent the progression of mild edema and might avoid or reduce the use of more invasive and expensive therapies. Excluding the fovea from the treated area does not seem to affect the results, which is of interest to novel laser practitioners.

Limited evidence suggests that the application of 670 nm of red light alters the course of aged decline. A previous report on 18 patients showed regression of drusen and improvement in visual functions in patients with intermediate age-related macular degeneration (AMD) by 12 months. We evaluated the functional and structural effects of applying 670 nm light to 31 patients with intermediate AMD and 11 people aged 55 years or above with normal retina. The study eyes were treated daily in the morning with a 670 nm hand-held light source housed in a torch-like tube that emitted energy equivalent to 40 mW/cm2 or 4.8J/ cm2 for 2 min at the viewing aperture. Visual function in terms of best-corrected visual acuity, low luminance visual acuity, scotopic thresholds and rod-intercept time were compared between baseline and 1, 3, 6 and 12 months. Structural changes on optical coherence tomography OCT and colour photographs were also assessed. Five withdrew consent voluntarily due to the intensity of the study visit assessments and two developed neovascular AMD and were excluded from further treatment and the analysis. In normal ageing, there was an improvement in scotopic thresholds in the group with no AMD by 1.77dB (p = 0.03) and no other parameters showed any clinically significant change. In eyes with intermediate AMD, there was no significant improvement in any functional or structural changes at any time point up to 12 months although the compliance was good. This pilot study shows that photobiomodulation with 670 nm has no effect in patients who have already progressed to intermediate AMD.

Purpose To prospectively evaluate whether diabetic macular ischemia detected with coherence tomography angiography (OCTA) is associated with change in functional outcomes over a period of one year. Methods This is a one-year prospective, observational study that included 56 eyes with varying levels of diabetic retinopathy. All participants underwent best corrected visual acuity evaluation, swept-source OCTA and microperimetry at baseline and repeated at one year. Parafoveal vessel densities (VD) and foveal avascular zone (FAZ) areas were generated from OCTA in the superficial and deep vascular plexuses. The influence of baseline and change in OCTA parameters on change in visual acuity and retinal sensitivity over one year was evaluated. Results Over the one-year follow-up period, 16% (9) of eyes had at least one line worsening in BCVA and 7% (4) of eyes had at least 5% decrease in retinal sensitivity compared to baseline. Diabetic retinopathy progressed in 12.5%. Mean superficial vascular plexus (SVP) FAZ area increased (0.32 ± 0.15 to 0.39 ± 0.18 mm2, P = 0.003) and parafoveal VD in deep vascular plexus (DVP) decreased (49.8 ± 3.7% to 48.8 ± 2.9%, P = 0.040) at one year compared to baseline. In the multivariate regression analysis, larger baseline DVP FAZ area was associated with worsening of BCVA over one year (β = 0.16 logMAR per mm2, 95% CI 0.02 to 0.31, P = 0.032). In addition, larger decreases in SVP VD (β = -4.18 db per 10% decrease, 95% CI -6.55 to -1.80, P = 0.002) was associated with worsening of retinal sensitivity over one year. Conclusions Progression of parafoveal microvasculature changes over one year can be detected using OCTA. Larger baseline DVP FAZ area on OCTA is predictive of worsening in visual outcomes, and larger decreases in SVP VD were associated with worsening of retinal sensitivity over a course of one year in diabetic individuals.

Purpose: To evaluate the safety and efficacy of dexamethasone intravitreal implant (Ozurdex, DEX implant) 0.7 and 0.35 mg in the treatment of patients with diabetic macular edema (DME).Design: Two randomized, multicenter, masked, sham-controlled, phase III clinical trials with identical protocols were conducted. Data were pooled for analysis.Participants: Patients (n = 1048) with DME, best-corrected visual acuity (BCVA) of 20/50 to 20/200 Snellen equivalent, and central retinal thickness (CRT) of ≥300 μm by optical coherence tomography.Methods: Patients were randomized in a 1:1:1 ratio to study treatment with DEX implant 0.7 mg, DEX implant 0.35 mg, or sham procedure and followed for 3 years (or 39 months for patients treated at month 36) at ≤40 scheduled visits. Patients who met retreatment eligibility criteria could be retreated no more often than every 6 months.Main Outcome Measures: The predefined primary efficacy endpoint for the United States Food and Drug Administration was achievement of ≥15-letter improvement in BCVA from baseline at study end. Safety measures included adverse events and intraocular pressure (IOP).Results: Mean number of treatments received over 3 years was 4.1, 4.4, and 3.3 with DEX implant 0.7 mg, DEX implant 0.35 mg, and sham, respectively. The percentage of patients with ≥15-letter improvement in BCVA from baseline at study end was greater with DEX implant 0.7 mg (22.2%) and DEX implant 0.35 mg (18.4%) than sham (12.0%; P ≤ 0.018). Mean average reduction in CRT from baseline was greater with DEX implant 0.7 mg (−111.6 μm) and DEX implant 0.35 mg (−107.9 μm) than sham (−41.9 μm; P < 0.001). Rates of cataract-related adverse events in phakic eyes were 67.9%, 64.1%, and 20.4% in the DEX implant 0.7 mg, DEX implant 0.35 mg, and sham groups, respectively. Increases in IOP were usually controlled with medication or no therapy; only 2 patients (0.6%) in the DEX implant 0.7 mg group and 1 (0.3%) in the DEX implant 0.35 mg group required trabeculectomy.Conclusions: The DEX implant 0.7 mg and 0.35 mg met the primary efficacy endpoint for improvement in BCVA. The safety profile was acceptable and consistent with previous reports.

Aims To characterise differential pathogeneses of diabetic macular oedema (DMO) using ultra-widefield fluorescein angiography (UWFA) and evaluate responses to anti-vascular endothelial growth factor (anti-VEGF) therapy. Methods Ninety-nine eyes (73 consecutive patients) with anti-VEGF naive DMO underwent UWFA and optical coherence tomography, of which 60 with central retinal thickness (CRT) >400 μm received monthly intravitreal ranibizumab injections. Best-corrected visual acuity (BCVA) and CRT were measured at baseline and after three injections. Results After excluding tractional factors, DMO was categorised into three types based on UWFA: (A) microaneurysm driven (49%), (B) peripheral ischaemia (37%) and (C) neovascularisation (15%). While all three types showed similar mean CRT (p=0.257), types B and C were associated with more diffuse oedema, which extended beyond the 6.0 mm central macula (p=0.0034). Following anti-VEGF treatment, all three types showed improvement in CRT and BCVA, which reached statistical significance for types A and B. A positive correlation was found between the Peripheral Ischaemia Index and improvement in CRT (slope=2.09, R 2 =0.1169, p=0.0151) but not BCVA (slope=−0.00037, R 2 =0.001149, p=0.8152). Conclusions UWFA facilitates the detection of peripheral ischaemia, which is associated with a significant proportion of DMO. While this group of DMO responded well to anti-VEGF therapy, it remains to be determined whether addressing the peripheral ischaemia may reduce recurrence.

Purpose The bradykinin 1 receptor may be important in inflammatory retinal vascular leakage in diabetic macular edema. BI 1026706 is an antagonist of bradykinin 1 receptor that has demonstrated efficacy in preclinical studies. Boehringer Ingelheim trial 1320.22 (NCT02732951) was a randomized, double-blind, placebo-controlled study. The pharmacodynamics, safety, and tolerability of oral BI 1026706 for 12 weeks were evaluated in patients with type 1 or type 2 diabetes mellitus and mild visual impairment owing to center-involved diabetic macular edema. Methods Patients (n = 105) were randomized to receive either oral BI 1026706 100 mg twice daily (morning and evening) or placebo for 12 weeks. The primary end point of the study was week 12 change from baseline in central subfield foveal thickness (CSFT) by spectral domain optical coherence tomography. Additional end points included absolute CSFT values, safety, and pharmacokinetics. Results After 12 weeks of treatment, there was no meaningful change from baseline in the adjusted mean CSFT in either treatment group (BI 1026706, 10.3 µm; placebo, -6.2 µm; adjusted mean treatment difference, 16.5 µm [95% confidence interval, -16.2 to 49.1]). There were also no differences in best-corrected visual acuity outcomes between treatment groups. Most reported adverse events were of mild or moderate intensity, and were balanced between treatment groups. Conclusions BI 1026706 was not superior to placebo in CSFT week-12 change from baseline. Therefore, BI 1026706 does not reduce CSFT, a morphologic sign of diabetic macular edema. Translational relevance Kinin-kallikrein inhibition effects may not be apparent over 12 weeks for bradykinin 1 receptor inhibition alone.

Purpose To evaluate the microstructure of the fovea in patients with familial exudative vitreoretinopathy (FEVR) compared to healthy controls using optical coherence tomography angiography (OCTA). Methods In this consecutive, cross-sectional, observational case series, 41 eyes of 41 patients diagnosed as FEVR and 37 eyes in 37 control subjects were studied. OCTA was utilized to automatically measure the foveal avascular zone (FAZ) and the vessel density (VD). Inner retinal thicknesses (IRT) and central retinal thickness (CRT) were measured with the instrument caliper. Targeted next-generation sequencing was performed, and phenotype-genotype association was analyzed. Results Small FAZ was found in 31.70% (13/41) FEVR eyes but not in controls. Greater CRT and lower superficial foveal VD were noted in FEVR patients. FAZ is negatively correlated with IRT. Persistence of the inner retinal layer (IRL) in fovea was present in 48.78% (20/41) FEVR eyes but not found in controls. Zero percent (0/10) of patients with the low-density lipoprotein receptor-related protein 5 (LRP5) mutation, 50% (1/2) with the frizzled-4 (FZD4) mutation, and 66.67% (3/4) with the tetraspanin-12 (TSPAN12) mutation had preserved foveal IRL and small FAZ. Conclusions Our data indicate FEVR status is associated with a significantly smaller FAZ, decreased vascular density in both the superficial and deep layers of parafoveal area, a thicker fovea, and an abnormally preserved IRL in fovea. In addition, patients with the LRP5 mutation had a milder phenotype than those with the FDZ4 or TSPAN12 mutations. These novel findings could provide insight into the understanding of the pathogenesis of FEVR.

Diabetic retinopathy, a complication of both type 1 and type 2 diabetes, is a complex disease and is one of the leading causes of blindness in adults worldwide. It can be divided into distinct subclasses, one of which is diabetic macular oedema. Diabetic macular oedema can occur at any time in diabetic retinopathy and is the most common cause of vision loss in patients with type 2 diabetes. The purpose of this review is to summarize the large number of genetic association studies that have been performed in cohorts of patients with type 2 diabetes and published in English-language journals up to February 2017. Many of these studies have produced positive associations with gene polymorphisms and diabetic retinopathy. However, this review highlights that within this large body of work, studies specifically addressing a genetic association with diabetic macular oedema, although present, are vastly under-represented. We also highlight that many of the studies have small patient numbers and that meta-analyses often inappropriately combine patient data sets. We conclude that there will continue to be conflicting results and no meaningful findings will be achieved if the historical approach of combining all diabetic retinopathy disease states within patient cohorts continues in future studies. This review also identifies several genes that would be interesting to analyse in large, well-defined cohorts of patients with diabetic macular oedema in future candidate gene association studies.

Purpose To evaluate the effect of intravitreal aflibercept injection on visual function in wet age-related macular degeneration (AMD). Design Prospective, multicenter, double-masked, active-controlled, parallel-group, randomized phase 3 clinical studies (VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD [VIEW] 1 and 2 [clinicaltrials.gov identifiers, NCT00509795 and NCT00637377, respectively]). Participants Patients (n = 2419) with active, treatment-naive, exudative AMD. This analysis included patients who received intravitreal aflibercept 2.0 mg every 8 weeks (2q8; n = 607) or ranibizumab 0.5 mg every 4 weeks (0.5q4; n = 595). Intervention Patients were randomized 1:1:1:1 to receive intravitreal aflibercept 2q8 (after 3 initial monthly doses), intravitreal aflibercept 2q4, intravitreal aflibercept 0.5q4, or ranibizumab 0.5q4 in the study eye. Patients in the intravitreal aflibercept 2q8 group received a sham injection alternating with active treatment. Main Outcome Measures The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was administered at baseline and at weeks 12, 24, 36, and 52. The NEI VFQ-25 subscale scores were compared between intravitreal aflibercept 2q8 and ranibizumab 0.5q4 treatment arms, the approved dosing for each agent worldwide. Change in composite NEI VFQ-25 score was evaluated based on categorical change in visual acuity (worsened, unchanged, improved). Results Baseline NEI VFQ-25 scores were similar for both treatments in both studies. Mean change from baseline to 52 weeks was similar for ranibizumab 0.5q4 and intravitreal aflibercept 2q8 across all 12 subscales, with the greatest improvements noted for mental health and general vision (9.0–11.6 points, both treatments, both studies). Improvement of 4 points or more (both treatments, both studies) also was observed for subscales near vision, distance vision, role difficulties, and dependency. Mean change from baseline to 52 weeks in NEI VFQ-25 composite score (pooled data) stratified by clinical response showed meaningful improvement only in patients who gained 5 Early Treatment Diabetic Retinopathy letters or more (7.3 and 7.8 points for intravitreal aflibercept 2q8 and ranibizumab 0.5q4, respectively). Conclusions Visual function outcomes were similar across all NEI VFQ-25 subscales over 52 weeks for intravitreal aflibercept 2q8 and ranibizumab 0.5q4, with clinically meaningful improvement recorded in 6 of 12 subscales.

Purpose To compare retinal sensitivity and central retinal thickness in patients with focal diabetic macular edema (DME) and edema secondary to branch retinal vein occlusion (BRVO). Methods In this consecutive, cross-sectional, observational study, patients with either DME or BRVO underwent measurements for best-corrected visual acuity, microperimetry, and spectral domain optical coherence tomography. Retinal thickness and sensitivity were measured using Optos Spectral optical coherence tomography/scanning laser ophthalmoscopy (Optos plc, Dunfermline, Scotland, United Kingdom). Areas defined as abnormal demonstrated edema with clearly defined cystic spaces. Abnormal and control areas were compared in mean retinal sensitivity and mean retinal thickness for both conditions. Results Twenty eyes with focal DME and nine eyes with BRVO were included. In DME, mean retinal thickness was 413.6 ± 84.5 μm and 291.7 ± 36.7 μm in abnormal and control areas, respectively. Mean retinal sensitivity was 10.22 ± 4.23 dB and 12.25 ± 3.57 dB, respectively. In BRVO, mean retinal thickness was 491.4 ± 102.9 μm and 315.9 ± 29.9 μm in abnormal and control areas, respectively. Mean retinal sensitivity was 6.36 ± 5.47 dB and 13.05 ± 2.28 dB. In DME, a decrease in retinal thickness of 0.341 μm correlated with 1 dB reduction of retinal sensitivity, although this was not statistically significant (P = 0.717). In BRVO, however, an increase in retinal thickness of 9.702 μm correlated with 1 dB reduction of retinal sensitivity (P = 0.001). Conclusion In BRVO, an increase in retinal thickness corresponded with a significant reduction in retinal sensitivity; in DME, however, there was no significant correlation between retinal thickness and retinal sensitivity. Further study is required to assess why this is the case. The Optos Spectral optical coherence tomography/scanning laser ophthalmoscopy allows for a reliable point-to-point correlation, as microperimetry and spectral domain optical coherence tomography can be performed in the same device.

To compare the efficacy of 50% threshold power with 25% threshold power of 577-nm subthreshold micropulse laser (SMPL) for acute central serous chorioretinopathy (CSC). Prospective, interventional, non-randomized, comparative case series. A total of 54 patients (54 eyes) with acute CSC were enrolled. Twenty-four eyes received 25% threshold power and 30 eyes received 50% threshold power of 577-nm SMPL. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and complete absorption of subretinal fluid (SRF) were evaluated at 1 month and 3 months. The complete absorption rate of SRF in the 50% power group was significantly greater than that in the 25% power group at 1 month (70.0% vs 25.0%, p

Introduction A large proportion of patients diagnosed with diabetic maculopathy using fundus photography and hence referred to specialist clinics following the current screening guidelines adopted in Hong Kong and United Kingdom are found to be false-positive, implying that they did not have macular oedema. This study aimed to evaluate the false-positive rate of diabetic maculopathy screening using the objective optical coherence tomography scan. Methods This was a cross-sectional observational study. Consecutive diabetic patients from the Hong Kong West Cluster Diabetic Retinopathy Screening Programme with fundus photographs graded R1M1 were recruited between October 2011 and June 2013. Spectral-domain optical coherence tomography imaging was performed. Central macular thickness of ≥300 μm and/or the presence of optical coherence tomography signs of diabetic macular oedema were used to define the presence of diabetic macular oedema. Patients with conditions other than diabetes that might affect macular thickness were excluded. The mean central macular thickness in various subgroups of R1M1 patients was calculated and the proportion of subjects with central macular thickness of ≥300 μm was used to assess the false-positive rate of this screening strategy. Results A total of 491 patients were recruited during the study period. Of the 352 who were eligible for analysis, 44.0%, 17.0%, and 38.9% were graded as M1 due to the presence of foveal 'haemorrhages', 'exudates', or 'haemorrhages and exudates', respectively. The mean (±standard deviation) central macular thickness was 265.1±55.4 μm. Only 13.4% (95% confidence interval, 9.8%-17.0%) of eyes had a central macular thickness of ≥300 μm, and 42.9% (95% confidence interval, 37.7%-48.1%) of eyes had at least one optical coherence tomography sign of diabetic macular oedema. For patients with retinal haemorrhages only, 9.0% (95% confidence interval, 4.5%-13.5%) had a central macular thickness of ≥300 μm; 23.2% (95% confidence interval, 16.6%-29.9%) had at least one optical coherence tomography sign of diabetic macular oedema. The false-positive rate of the current screening strategy for diabetic macular oedema was 86.6%. Conclusion The high false-positive rate of the current diabetic macular oedema screening adopted by the United Kingdom and Hong Kong may lead to unnecessary psychological stress for patients and place a financial burden on the health care system. A better way of screening is urgently needed. Performing additional spectral-domain optical coherence tomography scans on selected patients fulfils this need.

Microperimetry is a novel technique for assessing visual function that appears particularly suitable for age-related macular degeneration (AMD). Compared with standard automated perimetry, microperimetry offers several unique features. It simultaneously images the fundus, incorporates an eye-tracking system to correct the stimulus location for fixation loss, and identifies any preferred retinal loci. We identified 52 articles that met the inclusion criteria for a systematic review of microperimetry in the assessment of visual function in AMD. We discuss microperimetry and AMD in relation to disease severity, structural imaging outcomes, other measures of visual function, and evaluation of the efficacy of surgical and/or medical therapies in clinical trials. The evidence for the use of microperimetry in the functional assessment of AMD is encouraging. Disruptions of the ellipsoid zone band and retinal pigment epithelium are clearly associated with reduced differential light sensitivity despite the maintenance of good visual acuity. Reduced differential light sensitivity is also associated with outer segment thinning and retinal pigment epithelium thickening in early AMD and with both a thickening and a thinning of the whole retina in choroidal neovascularization. Microperimetry, however, lacks the robust diffuse and focal loss age-corrected probability analyses associated with standard automated perimetry, and the technique is currently limited by this omission.

Purpose To evaluate the efficacy and safety of sequential therapy with ranibizumab followed by dexamethasone intravitreal implant compared with dexamethasone monotherapy for macular oedema (MO) secondary to retinal vein occlusion (RVO). Methods In this retrospective interventional study, the medical records of subjects with MO due to RVO who received either ranibizumab followed by dexamethasone intravitreal implant (Group 1) or dexamethasone-implant monotherapy (Group 2) were included. Primary outcome was the proportion of subjects who exhibited best-corrected visual acuity (VA) gain and resolution of MO within 6 months. Results Thirty-three eyes were included (17 in Group 1, 16 in Group 2). More subjects in Group 1 exhibited a VA gain of at least 0.5 (LogMAR units hereafter) than Group 2 (29% vs 0%, p=0.044). The speed of VA gain was greater in Group 1 (1.4±0.8 months vs 2.7±1.4 months, p=0.020). MO was controlled in more subjects in Group 1 at all measured time intervals, and this difference was statistically significant at 3 months and 4 months. Subjects with branch RVO experienced VA gain more rapidly if they were from Group 1 (p=0.023). Conclusions Sequential therapy was found to be more effective than dexamethasone monotherapy in treating MO due to RVO. © 2014 by the BMJ Publishing Group Ltd.

Background/aims To evaluate efficacy and safety of intravitreal aflibercept (IVT-AFL) in Japanese patients with wet age-related macular degeneration (wAMD) from the VIEW 2 trial. Methods In this double-masked study, patients were randomised to: 0.5 mg IVT-AFL every 4 weeks (0.5q4); 2 mg IVT-AFL every 4 weeks (2q4); 2 mg IVT-AFL every 8 weeks (2q8) after 3 monthly injections; or 0.5 mg ranibizumab every 4 weeks (Rq4). Main efficacy outcomes included vision maintenance and best-corrected visual acuity (BCVA) at week 52. Results At week 52, all Japanese patients in the IVT-AFL groups (n=70) maintained vision, compared with 96% of Japanese patients (n=23/24) treated with ranibizumab. Japanese patients in all treatment groups showed improvement in BCVA after treatment. The Rq4, 2q4 and 2q8 groups experienced similar gains in BCVA from baseline. The 0.5q4 group had higher gains due to an unexpected drop in BCVA between screening and baseline. Central retinal thickness and mean area of choroidal neovascularisation decreased in all treatment groups with similar magnitude. Ocular treatment-emergent adverse events were balanced across treatment groups. Conclusions IVT-AFL was effective and well tolerated in Japanese patients. Outcomes in this population were consistent with those in the overall VIEW 2 population. Trial registration number NCT00637377.

Robert M J Purbrick, Shahrnaz Izadi, Ankur Gupta, N Victor Chong Oxford Eye Hospital, John Radcliffe Hospital, Oxford, UK Purpose: We aimed to assess the agreement between clinical assessment of diabetic retinopathy and Optomap ultrawide-field imaging (UWFI) in a real-life clinic setting. Methods: Structured examination findings, from diabetic patients attending routine medical retina clinics in July 2011, were retrospectively compared with the grade obtained from Optomap UWFI images, graded independently by two ophthalmologists, taken at the same visit. Results: A total of 84 eyes (42 patients) were examined, and 74 eyes (37 patients) were suitable for analysis. The hospital Eye Service slit-lamp biomicroscopy grades for retinopathy were: no diabetic retinopathy in zero eyes; background retinopathy in 21 eyes; preproliferative retinopathy in 34 eyes; and proliferative retinopathy in 19 eyes. For retinopathy, the agreement between the Optomap UWFI and clinical grading was moderate for both graders (κ=0.57 and κ=0.63), and there was almost perfect agreement between the two graders (κ=0.92). The clinical grades for the presence of photocoagulation scars were: no photocoagulation scars in 46 eyes and photocoagulation scars visible in 28 eyes, indicating substantial agreement between the Optomap UWFI and clinical grading for both graders (κ=0.73 and κ=0.64). There were two instances where proliferative retinopathy was documented clinically but graded as preproliferative by both graders of Optomap UWFI. These were investigated, and neither patient required treatment, ie, the difference in retinopathy grade would not have affected the patient outcomes. Conclusion: This study demonstrated moderate agreement between Optomap UWFI and hospital slit-lamp biomicroscopy grading of patients’ retinopathy in a real-life medical retina clinic setting. The authors believe that Optomap UWFI is, not only a very useful adjunct to clinical examination in terms of detection and recording of retinopathy, but also, could have a role in standalone “virtual” clinics. Keywords: photography

Purpose: To determine efficacy and safety of intravitreal aflibercept in patients with neovascular age-related macular degeneration (AMD) during a second year of variable dosing after a first-year fixed-dosing period. Design: Two randomized, double-masked, active-controlled, phase 3 trials. Participants: Two thousand four hundred fifty-seven patients with neovascular AMD. Methods: From baseline to week 52, patients received 0.5 mg intravitreal ranibizumab every 4 weeks (Rq4), 2 mg aflibercept every 4 weeks (2q4), 0.5 mg aflibercept every 4 weeks (0.5q4), or 2 mg aflibercept every 8 weeks (2q8) after 3 monthly injections. During weeks 52 through 96, patients received their original dosing assignment using an as-needed regimen with defined retreatment criteria and mandatory dosing at least every 12 weeks. Main Outcome Measures: Proportion of eyes at week 96 that maintained best-corrected visual acuity (BCVA; lost

Purpose: The “traffic light” color designation of differential light sensitivity used in a number of microperimeters does not encompass the conventional Total and Pattern Deviation probability analyses adopted by standard automated perimetry. We determined whether the color designation is indicative of abnormality as represented by the “gold standard” Pattern Deviation probability analysis. Methods: Total and Pattern Deviation probability levels, using two different methods, were derived at each of 40 stimulus locations, within 7° eccentricity, from 66 ocular healthy individuals (66 eyes) who had undergone microperimetry with the Macular Integrity Assessment microperimeter. The probability levels were applied to the corresponding fields from each of 45 individuals (45 eyes) with age-related macular degeneration (AMD) and evaluated in relation to the color designation. Results: Sensitivities designated in orange encompassed the entire range of Pattern Deviation probability levels (from normal to P ≤ 1%). Those designated in green were mostly normal; those in red/black generally corresponded to the ≤1% probability level. Conclusions: The green and the red/black designations are generally indicative of normal and abnormal probability values, respectively. The orange designation encompassed all probability outcomes and should not be relied upon for visual field interpretation. The evidence base indicates replacement of the color designation of sensitivity in AMD by Total Deviation and Pattern Deviation analyses. Translational Relevance: The use of Total and Pattern Deviation probability analyses is not universal in all microperimeters, and the derivation of these values indicates that color coding will lead to errors in evaluating visual field loss.

Purpose To assess anatomic and visual outcomes of ocriplasmin use for symptomatic vitreomacular adhesion (VMA). Design Retrospective chart review. Methods Macula Society members were surveyed online to collect data on ocriplasmin for symptomatic VMA. Clinical and optical coherence tomography data were collected using standardized data entry forms. Results There were 208 patients (208 eyes) with symptomatic VMA followed at least 3 weeks after receiving ocriplasmin. At baseline, VMA was focal (

Previous studies have shown that patients with diabetic macular edema (DME) with relatively good visual acuity can have slow reading speed. The aim of this study was to evaluate the structural-functional correlation in a cohort of patients with DME and to assess whether the central four retinal points on microperimetry (MP4) could be used as a potentially faster and more reliable method of assessing retinal function in patients with DME than reading speed.The study was performed on patients with clinically significant DME. The best-corrected visual acuity (BCVA) was recorded with letter counting on a modified ETDRS chart, the maximal reading speed (MRS) was recorded with MNREAD, the retinal sensitivity (MP28 and MP4) was measured with Optos OCT/ Scanning Laser Ophthalmoscopy and the central subfield thickness was measured by Heidelberg Spectralis Spectral Domain Optical Coherent Topography.Of 100 eyes analyzed, 76 eyes were included in the study. The mean BCVA was 76.5 letters (Snellen equivalent 6/18), the mean MRS was 156.8 words per minute, the mean MP4 was 9.81 dB per point, and the mean central subfield thickness was 309.3 microns. It was found that faster MRS is correlated with younger age (P = 0.001), better BCVA (P0.0001), and better retinal sensitivity (P0.0001) for both MP28 and MP4, but not with central subfield thickness (P = 0.66). Central subfield thickness is correlated with MP28 (P = 0.05) but not with age (P = 0.812), BCVA (P = 0.113), or MP4 (P = 0.485). After correction for age and BCVA, MRS is still correlated with MP28 (P = 0.001) and MP4 (P = 0.015).Patients with DME can have reduced reading speed despite good visual acuity. Maximal reading speed is often reported to be difficult to perform, inconsistent, and affected by language and educational level. However, in this study, the authors found that the central MP4 points are quick and easy to test in most of the patients, and are highly correlated with MRS. Microperimetry might therefore represent a useful additional functional test that could be considered better than BCVA or reading speed in quantifying visual function in patients with DME.

Recent clinical trials have changed the management paradigm for diabetic macular edema (DME). There is an urgent need to identify the most effective ways of preventing retinopathy or intervening at an early, asymptomatic stage in order to preserve vision. The rise in the incidence of diabetes is a serious public health concern. Grading and screening programmes help to identify sight threatening diabetic retinopathy in the community early and facilitate timely referral to an ophthalmologist. Systemic therapies for DME target the key modifiable risk factors: metabolic and blood pressure control. There may also be a role for modification of the renin-angiotensin system and for lipid lowering agents. Improved glycemic and blood pressure control remain the most effective ways of reducing morbidity from DME. Fenofibrate also has beneficial effects, but the mechanism for this remains unclear. Multiple new treatments are in the pipeline, and these are expected to change our approach to DME for the first time in 30 years.

Vascular endothelial growth factor (VEGF) plays an important role in the pathophysiology of several sight-threatening retinal disorders such as age-related macular degeneration, diabetic macular edema and proliferative diabetic retinopathy. The discovery of anti-VEGF agents has revolutionized our treatment of these conditions. There are 4 anti-VEGF agents that are either approved or in common use in ophthalmology, namely pegaptanib (Macugen, Pfizer), ranibizumab (Lucentis, Novartis), aflibercept or VEGF Trap-Eye (EYLEA, Bayer) and bevacizumab (Avastin, Roche). There are differences between them. In this review, the differences are discussed in detail. Furthermore, an attempt is made to explain some of the clinical trial data based on their differences in ocular efficacy, duration of action, and local and systemic safety concerns.

Background/aims:\ud Retinal screening programmes in England and Scotland have similar photographic grading schemes for background (non-proliferative) and proliferative diabetic retinopathy, but diverge over maculopathy. We looked for the most cost-effective method of identifying diabetic macular oedema from retinal photographs including the role of automated grading and optical coherence tomography, a technology that directly visualises oedema. \ud \ud Methods: Patients from seven UK centres were recruited. The following features in at least one eye were required for enrolment: microaneurysms/dot haemorrhages or blot haemorrhages within one disc diameter, or exudates within one or two disc diameters of the centre of the macula. Subjects had optical coherence tomography and digital photography. Manual and automated grading schemes were evaluated. Costs and QALYs were modelled using microsimulation techniques. \ud \ud Results: 3540 patients were recruited, 3170 were analysed. For diabetic macular oedema, England’s scheme had a sensitivity of 72.6% and specificity of 66.8%; Scotland’s had a sensitivity of 59.5% and specificity of 79.0%. When applying a ceiling ratio of £30 000 per quality adjusted life years (QALY) gained, Scotland’s scheme was preferred. Assuming automated grading could be implemented without increasing grading costs, automation produced a greater number of QALYS for a lower cost than England’s scheme, but was not cost effective, at the study’s operating point, compared with Scotland’s. The addition of optical coherence tomography, to each scheme, resulted in cost savings without reducing health benefits. \ud \ud Conclusions: Retinal screening programmes in the UK should reconsider the screening pathway to make best use of existing and new technologies.

Association with risk factors for arterial disease confirms current theory of pathogenesis Retinal vein occlusion is one of the most common causes of sudden painless unilateral loss of vision. It is the second most common retinal vascular disease after diabetic retinopathy.1 Occlusion may occur in the central retinal vein or branch retinal vein. Although specific ocular risk factors for central retinal vein occlusion include increased intraocular pressure and anatomical variation of the optic disc, systemic risk factors occur in patients with both types of occlusion.2 3 In a linked case-control study based on data from Danish national registries (doi:10.1136/bmj.e7885), Bertelsen and colleagues investigated comorbidity in patients with branch retinal vein occlusion.4 They were wise to study only patients with branch retinal vein occlusion because patients with central retinal vein occlusion may have ocular risk factors, so combining patients with both types of occlusion in one study of systemic risk factors could bias the findings. Patients with retinal vein occlusion usually present with sudden loss of vision in …

PURPOSE: Fundus autofluorescence (FAF), as an index of lipofuscin accumulation in the retinal pigment epithelium (RPE), provides indirect information on the level of metabolic activity of the RPE and thus the integrity of the RPE/photoreceptor complex. To investigate whether the photoreceptor/RPE complex is still viable in patients with Leber congenital amaurosis (LCA), FAF imaging was performed. METHODS: Three patients with LCA (patients A, B, and C; ages, 24, 15, and 37 years, respectively) were enrolled and one patient with RP with preserved visual acuity (age, 28 years) was included as a control. The diagnosis was based on history, visual function, and Ganzfeld electroretinography (International Society for Clinical Electrophysiology of Vision [ISCEV] standard). FAF was recorded with a confocal scanning laser ophthalmoscope (cSLO; Heidelberg Retina Angiograph; Heidelberg Engineering, Heidelberg, Germany). RESULTS: All patients with LCA had vision reduced to perception of light and had undetectable ERGs. FAF was normal in patient A. In patient B, there was a parafoveal ring of mildly increased FAF. The midperiphery showed mildly decreased FAF. Patient C showed a parafoveal ring of moderately increased FAF. FAF was moderately decreased along the arcades and the midperiphery. The patient with RP showed a parafoveal ring of moderately increased FAF and severely decreased FAF eccentric to the macula including the periphery. CONCLUSIONS: The FAF findings in these patients with LCA suggest that there is continuous metabolic demand from the photoreceptors and that the RPE/photoreceptor complex is, at least in part, anatomically intact, but the photoreceptors have lost function. These findings may have implications for future treatment. It is notable that more than 20 years of severe visual impairment associated with LCA can be associated with normal FAF, indicating that photoreceptor function may be rescuable.